<i>IGFBP5</i> Promotes Atherosclerosis in APOE<sup>−/−</sup> Mice Through Phenotypic Transformation of VSMCs
Atherosclerosis constitutes a pathological process underlying cardiovascular diseases. There is growing evidence that <i>IGFBP5</i> is a causative factor, although the conclusions of different studies are inconsistent. The present study aims to confirm the role and mechanism of <i>...
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2025-07-01
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| author | Aoqi Xiang Hua Guan Peihong Su Lusha Zhang Xiaochang Chen Qi Yu |
| author_facet | Aoqi Xiang Hua Guan Peihong Su Lusha Zhang Xiaochang Chen Qi Yu |
| author_sort | Aoqi Xiang |
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| description | Atherosclerosis constitutes a pathological process underlying cardiovascular diseases. There is growing evidence that <i>IGFBP5</i> is a causative factor, although the conclusions of different studies are inconsistent. The present study aims to confirm the role and mechanism of <i>IGFBP5</i> in atherosclerosis. The expression of <i>IGFBP5</i> was induced in the skeletal muscle of male ApoE<sup>−/−</sup> mice, an atherosclerosis model, using adeno-associated virus, resulting in elevated circulating <i>IGFBP5</i> levels. Changes in blood lipids were detected, and pathological changes in the aorta were observed. Analysis of <i>IGFBP5</i> function using RNA sequencing and validation were performed in a mouse aortic smooth muscle cell line. The results demonstrated that <i>IGFBP5</i> overexpression exacerbated the development of aortic lesions in this murine models without any discernible alterations in lipid profile parameters; the arterial transcriptomic landscape revealed that heightened <i>IGFBP5</i> levels predominantly influenced pathways governing smooth muscle cell proliferation and motility. In vitro experimentation corroborated these findings, showcasing the stimulatory effect of <i>IGFBP5</i> on VSMC (vascular smooth muscle cell) proliferation and migration, provoking a transition toward a proliferative phenotype. <i>IGFBP5</i> promotes atherosclerosis in ApoE<sup>−/−</sup> mice through the phenotypic transformation of VSMCs. This finding suggests that <i>IGFBP5</i> has the potential to serve as an indicator of atherosclerosis diagnosis and a target for therapeutic interventions in the future. |
| format | Article |
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| institution | Kabale University |
| issn | 1467-3037 1467-3045 |
| language | English |
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| spelling | doaj-art-dcf23734f5a048efb8080fb3069a467c2025-08-20T03:58:31ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452025-07-0147755510.3390/cimb47070555<i>IGFBP5</i> Promotes Atherosclerosis in APOE<sup>−/−</sup> Mice Through Phenotypic Transformation of VSMCsAoqi Xiang0Hua Guan1Peihong Su2Lusha Zhang3Xiaochang Chen4Qi Yu5Shaanxi Key Laboratory of Ischaemic Cardiovascular Diseases & Institute of Basic and Translational Medicine, Xi’an Medical University, Xi’an 710021, ChinaShaanxi Key Laboratory of Ischaemic Cardiovascular Diseases & Institute of Basic and Translational Medicine, Xi’an Medical University, Xi’an 710021, ChinaShaanxi Key Laboratory of Ischaemic Cardiovascular Diseases & Institute of Basic and Translational Medicine, Xi’an Medical University, Xi’an 710021, ChinaShaanxi Key Laboratory of Ischaemic Cardiovascular Diseases & Institute of Basic and Translational Medicine, Xi’an Medical University, Xi’an 710021, ChinaShaanxi Key Laboratory of Ischaemic Cardiovascular Diseases & Institute of Basic and Translational Medicine, Xi’an Medical University, Xi’an 710021, ChinaShaanxi Key Laboratory of Ischaemic Cardiovascular Diseases & Institute of Basic and Translational Medicine, Xi’an Medical University, Xi’an 710021, ChinaAtherosclerosis constitutes a pathological process underlying cardiovascular diseases. There is growing evidence that <i>IGFBP5</i> is a causative factor, although the conclusions of different studies are inconsistent. The present study aims to confirm the role and mechanism of <i>IGFBP5</i> in atherosclerosis. The expression of <i>IGFBP5</i> was induced in the skeletal muscle of male ApoE<sup>−/−</sup> mice, an atherosclerosis model, using adeno-associated virus, resulting in elevated circulating <i>IGFBP5</i> levels. Changes in blood lipids were detected, and pathological changes in the aorta were observed. Analysis of <i>IGFBP5</i> function using RNA sequencing and validation were performed in a mouse aortic smooth muscle cell line. The results demonstrated that <i>IGFBP5</i> overexpression exacerbated the development of aortic lesions in this murine models without any discernible alterations in lipid profile parameters; the arterial transcriptomic landscape revealed that heightened <i>IGFBP5</i> levels predominantly influenced pathways governing smooth muscle cell proliferation and motility. In vitro experimentation corroborated these findings, showcasing the stimulatory effect of <i>IGFBP5</i> on VSMC (vascular smooth muscle cell) proliferation and migration, provoking a transition toward a proliferative phenotype. <i>IGFBP5</i> promotes atherosclerosis in ApoE<sup>−/−</sup> mice through the phenotypic transformation of VSMCs. This finding suggests that <i>IGFBP5</i> has the potential to serve as an indicator of atherosclerosis diagnosis and a target for therapeutic interventions in the future.https://www.mdpi.com/1467-3045/47/7/555atherosclerosis<i>IGFBP5</i>ApoE<sup>−/−</sup> miceVSMCsphenotypic transformation |
| spellingShingle | Aoqi Xiang Hua Guan Peihong Su Lusha Zhang Xiaochang Chen Qi Yu <i>IGFBP5</i> Promotes Atherosclerosis in APOE<sup>−/−</sup> Mice Through Phenotypic Transformation of VSMCs Current Issues in Molecular Biology atherosclerosis <i>IGFBP5</i> ApoE<sup>−/−</sup> mice VSMCs phenotypic transformation |
| title | <i>IGFBP5</i> Promotes Atherosclerosis in APOE<sup>−/−</sup> Mice Through Phenotypic Transformation of VSMCs |
| title_full | <i>IGFBP5</i> Promotes Atherosclerosis in APOE<sup>−/−</sup> Mice Through Phenotypic Transformation of VSMCs |
| title_fullStr | <i>IGFBP5</i> Promotes Atherosclerosis in APOE<sup>−/−</sup> Mice Through Phenotypic Transformation of VSMCs |
| title_full_unstemmed | <i>IGFBP5</i> Promotes Atherosclerosis in APOE<sup>−/−</sup> Mice Through Phenotypic Transformation of VSMCs |
| title_short | <i>IGFBP5</i> Promotes Atherosclerosis in APOE<sup>−/−</sup> Mice Through Phenotypic Transformation of VSMCs |
| title_sort | i igfbp5 i promotes atherosclerosis in apoe sup sup mice through phenotypic transformation of vsmcs |
| topic | atherosclerosis <i>IGFBP5</i> ApoE<sup>−/−</sup> mice VSMCs phenotypic transformation |
| url | https://www.mdpi.com/1467-3045/47/7/555 |
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